Coarse-grained implicit solvent lipid force field with a compatible resolution to the Cα protein representation

Area of Science:

• Computational biophysics
• Molecular dynamics simulations
• Membrane biophysics

Background:

• Coarse-grained (CG) molecular dynamics simulations are crucial for studying biological membranes.
• Existing CG lipid models are either too simple (3 beads) or too complex (>10 beads).
• A need exists for CG lipid models with resolution compatible with residue-level CG protein models.

Purpose of the Study:

• To extend a three-bead lipid model to a five-bead model (iSoLF) for phospholipids.
• To parameterize the iSoLF model for POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine).
• To evaluate the model's ability to reproduce key membrane properties and dynamics.

Main Methods:

• Extension of a pre-existing three-bead CG lipid model to a five-bead model.
• Parameterization of the iSoLF model for POPC and DPPC phospholipids.
• Molecular dynamics simulations to assess area per lipid, hydrophobic thickness, phase behavior, bilayer formation, temperature dependence, vesicle dynamics, and two-component membrane dynamics.

Main Results:

• The iSoLF model successfully reproduced the area per lipid, hydrophobic thickness, and phase behaviors of POPC and DPPC membranes at physiological temperatures.
• Simulated POPC membranes were in the liquid phase and DPPC membranes in the gel phase, consistent with experimental data.
• The model demonstrated promising results for spontaneous bilayer formation, temperature-dependent properties, vesicle dynamics, and POPC/DPPC mixture dynamics.

Conclusions:

• The developed iSoLF five-bead CG lipid model provides a suitable resolution for simulating phospholipid bilayers.
• This model shows promise for accurately capturing essential membrane physical properties and dynamic behaviors.
• The iSoLF model, when integrated with standard Cα protein models, will be a valuable tool for simulating complex biological membrane systems involving both lipids and proteins.